We will continue working on the title project by examining more closely the effects of the convulsant agent methionine sulfoximine (MSO) on cerebral methylations. Several avenues will be followed. We will test whether the administration of MSO induces the establishment in brain tissue of abnormal ratios of S-adenosyl methionine (SAM) to S- adenosyl homocysteine (SAH) and for this we are developing a sensitive, isotopic assay for SAH. In addition, we aim to determine whether nervous tissue of MSO-treated animals contains larger amounts of methylated amines than does normal tissue. We shall also examine the possibility that MSO affects methylation of transfer ribonucleic acids ( RNA) and to do this we shall determine the capacity to be methylated and the resulting profile of methylated bases of RNAs isolated from control and MSO-treated brains. We also plan to examine the effect of the known MSO-induced reduction of cerebral SAM levels on the in situ profile of methylated ribosomal RNA (rRNA), by comparing methylated sites in rRNA after administration in vivo of radioactive methionine to control and MSO-treated animals. The study of interactions of MSO with serotonin metabolism and turnover will also be continued.